A system for investigating oesophageal photoplethysmographic signals in anaesthetised patients

The monitoring of arterial blood oxygen saturation in patients with compromised peripheral perfusion is often difficult, because conventional non-invasive techniques such as pulse oximetry (SpO2) can fail. Poor peripheral circulation commonly occurs after major surgery including cardiopulmonary bypass. The difficulties in these clinical situations might be overcome if the sensor were to monitor a better perfused central part of the body such as the oesophagus. A new oesophageal photoplethysmographic (PPG) probe and an isolated processing system have been developed to investigate the pulsatile signals of anaesthetised adult patients undergoing routine surgery. Measurements were made in the middle third of the oesophagus, 25 cm to 30 cm from the upper incisors. The AC PPG signals are sampled by a data acquisition system connected to a laptop computer. The signals recorded correspond to infrared and red AC PPGs from the middle third oesophagus and the finger. Preliminary results from 20 patients show that good quality AC PPG signals can be measured in the human oesophagus. The ratio of the oesophageal to finger AC PPG amplitudes was calculated for the infrared and red wavelengths for each patient. The mean (+/- standard deviation) of this ratio was 2.9 +/- 2.1 (n = 19) for the infrared wavelength and 3.1 +/- 2.4 (n = 16) for the red wavelength. The red and infrared wavelengths used are appropriate for pulse oximetry and this investigation indicates that the mid-oesophagus may be a suitable site for the reliable monitoring of SpO2 in patients with poor peripheral perfusion.     

Non-invasive measurement of systolic blood pressure on the arm utilising photoplethysmography: development of the methodology

Photoplethysmography (PPG) can be used to measure systolic blood pressure at the brachial artery. With a specially designed probe, positioned in the most distal position beneath a pressure cuff on the upper arm, this is possible. The distance between the light source (880 nm) and the photodetector was 20 mm. A test was performed on neuro-intensive care patients by determining blood pressure from the PPG curves, and, when it was compared with systolic blood pressure obtained from inserted indwelling arterial catheters, a correlation factor of r=0.95 was achieved. The difference between blood pressure obtained using PPG and invasive blood pressure measurement was 3.9±9.1 mmHg (mean±SD), n=19. The depth to the brachial artery was 13.9±4.1 mm (mean±SD), n=18. A digital PPG system utilising pulsating light was also developed.     

A system for investigating oesophageal photoplethysmographic signals in anaesthetised patients

The monitoring of arterial blood oxygen saturation in patients with compromised peripheral perfusion is often difficult, because conventional noninvasive techniques such as pulse oximetry (SpO₂) can fail. Poor peripheral circulation commonly occurs after major surgery including cardiopulmonary bypass. The difficulties in these clinical situations might be overcome if the sensor were to monitor a better perfused central part of the body such as the oesophagus. A new oesophageal photoplethysmographic (PPG) probe and an isolated processing system have been developed to investigate the pulsatile signals of anaesthetised adult patients undergoing routine surgery. Measurements were made in the middle third of the oesophagus, 25 cm to 30 cm from the upper incisors. The AC PPG signals are sampled by a data acquisition system connected to a laptop computer. The signals recorded correspond to infrared and red AC PPGs from the middle third oesophagus and the finger. Preliminary results from 20 patients show that good quality AC PPG signals can be measured in the human oesophagus. The ratio of the oesophageal to finger AC PPG amplitudes was calculated for the infrared and red wavelengths for each patient. The mean (±standard deviation) of this ratio was 2.9±2.1 (n=19) for the infrared wavelength and 3.1±2.4 (n=16) for the red wavelength. The red and infrared wavelengths used are appropriate for pulse oximetry and this investigation indicates that the mid-oesophagus may be a suitable site for the reliable monitoring of SpO₂ in patients with poor peripheral perfusion.     

Interaction of sympathetic vasoconstriction and antidromic vasodilatation in the control of skin blood flow

 We studied the interaction between the vasoconstriction evoked by postganglionic sympathetic neurones (sympathetic vasoconstriction) and the vasodilatation mediated by small-diameter afferent neurones (antidromic vasodilatation) in hairless skin of anaesthetized rats kept under controlled conditions. In all animals both the lumbar sympathetic trunk (LST) and the ipsilateral dorsal root (DR) L5 were surgically exposed, sectioned and electrically stimulated using different protocols. This experimental approach results in the exclusive and selective activation of sympathetic efferents and primary afferents respectively. Blood flow responses were measured using laser Doppler flowmetry. Sectioning the LST resulted in a pronounced increase in cutaneous blood flow by 112±15% (mean±SEM, n=25) indicating that ongoing sympathetic vasoconstrictor activity had been abolished. When a brief antidromic vasodilatation was produced by DR stimulation with 10–15 pulses at 1 Hz with C-fibre intensity during a sustained sympathetic vasoconstriction, peak blood flow reached preconstriction levels at LST stimulation frequencies of ≤3 Hz. By contrast, antidromic vasodilatation was reduced at sympathetic stimulation frequencies of ≥5 Hz and absent when stimulating the LST with 20 Hz. A similar response characteristic was obtained when LST and DR stimulation were started simultaneously. Continuous DR stimulation with 0.1 Hz evoked a substantial increase in cutaneous blood flow by 38±10% (mean±SEM, n=8) to a new baseline level. When sympathetic vasoconstriction was elicited on this background DR stimulation, the responses were smaller at all sympathetic frequencies. However, the maximum decrease in blood flow was significantly smaller than the controls at LST stimulation with ≤3 Hz but not at higher frequencies. We conclude that sympathetic vasoconstriction and antidromic vasodilatation are competitive influences in the control of cutaneous blood flow. At low levels of cutaneous sympathetic vasoconstrictor activity, which probably prevail under resting conditions in the absence of cold stress, antidromic vasodilatation overrides sympathetic vasoconstriction. At high levels of cutaneous sympathetic activity, which may be reached in normal life under the conditions of severe cold, sympathetic vasoconstriction can suppress antidromic vasodilatation almost totally. Received: 24 April 1996 / Accepted: 3 September 1996     

Glottis constriction response in healthy subjects

The purpose of this study was to evaluate the glottis constriction response induced by a sudden and involuntary increase in gastric and oesophageal pressures by Tll-Ll intervertebral magnetic stimulation of the abdominal muscle roots in nine healthy subjects. Twitch flow, twitch gastric, and oesophageal pressures were measured after abdominal muscle root stimulation, which allowed pharyngo-laryngeal muscle activation to be characterized. Pharyngeal endoscopies were performed on five subjects to assess vocal cord movements. All stimulations induced positive gastric and oesophageal pressures and expiratory flow, which increased with stimulation intensity (flow: R=0.32; p<0.0001; oesophageal pressure: R=0.26; p=0.001; gastric pressure: R=0.37; p<0.0001). Twitch gastric pressure and twitch oesophageal pressure were negatively correlated with twitch flow (respectively, R=-0.183, p<0.05; R=-0.35, p<0.0001). Upper airway resistance was higher at peak oesophageal pressure than at peak flow (p<0.001). Peak twitch gastric and twitch oesophageal pressure latencies were similar (133+/-4ms and 122+/-4ms) but longer than peak twitch flow and EMG latencies (62+/-2ms and 73+/-4ms, p<0.0001). Glottis constriction following magnetic abdominal muscle root stimulation was seen in all subjects during endoscopy, with a latency estimated at between 80 and 100ms. This method could be a new, simple tool for assessing the upper airway constriction protective reflex.     

Effects of muscle blood flow on muscle energy metabolism and contractility

Energy metabolism and contractility of rat’s femoral triceps muscles were investigated by varying blood flow levels with ligation of the femoral artery. The triceps were stimulated electrically to produce equivalent conditions as exercise loading, and phosphorus nuclear magnetic resonance (³¹P-NMR) spectra and muscle tension levels were monitored. The ratio of inorganic phosphate (Pi) to ‘Pi+phosphocreatine (PCr)’, i.e. Pi/(Pi+PCr), was obtained from ³¹P-NMR spectra. This ratio was related to the reduction of blood flow ratio (BFR) during and after the stimulation period, whereas before starting the stimulation, there was no significant correlation. These findings indicate: (i) muscle energy metabolism during decreased blood flow is influenced by the stimulation (loading) given to the muscle; and (ii) changes of muscle energy metabolism due to decreased muscle blood flow during the loading is evaluable by measuring ³¹P-NMR spectra. Muscle tension reached the plateau 8 min after starting the stimulation, regardless of BFR, but muscle tension ratio decreased as BFR became lower. This indicates that decreased blood flow diminishes muscle contractility, and then lowers muscle function levels. Our findings indicate that muscle blood flow plays an important role in muscle function, and blood flow and muscle function levels are evaluable by measuring ³¹P-NMR spectra of the muscle.     

A non-invasive measure of changes in blood flow in the human anterior tibial muscle

We used photoplethysmography (PPG) to monitor blood flow changes in the human anterior tibial muscle during arterial occlusion and during isometric and concentric contractions. Single-fibre laser-Doppler flowmetry (LDF) was used as a reference in 12 healthy subjects (5 men, 7 women; mean age 24 years). Post-exercise hyperaemic muscle blood flow (MBF) was measured immediately after isometric dorsiflexion of the ankle joint at maximal contraction for 1 min and full range-of-motion dorsiflexion and plantar flexion of the ankle joint for 1 min. A thigh tourniquet was applied for the evaluation of post-occlusive reactive hyperaemia. The MBF (baseline=100%) was [mean (SD)] 150 (31)% (P=0.003) by PPG (880 nm) and 182 (66)% (P=0.012) by LDF. After 1 min of maximal isometric contraction, MBF increased to 150 (51)% (P=0.003) by PPG (880 nm) and to 169 (43)% (P=0.005) by LDF. After 1 min of maximal concentric contractions, MBF increased to 158 (59)% (P=0.003) by PPG (880 nm) and to 170 (99)% (P=0.008) by LDF. Skin blood flow, PPG (560 nm), did not change significantly after isometric or concentric contractions. The results indicate that reactive hyperaemia after exercise and arterial occlusion can be assessed in the human anterior tibial muscle using PPG. Electronic Publication     

Functional significance of collateral blood flow in working skeletal muscle of the dog

Summary The semitendinosus muscle of the dog is supplied by two separate arteries and drained by two corresponding veins. In the muscles used in this study no blood entering via the distal artery was found to leave via the proximal vein during perfusion through both arteries (orthograde perfusion). Therefore, collateral flow (CF) could be determined as proximal venous outflow during occlusion of the proximal artery. During orthograde perfusion total blood flow averaged 12 ml × min⁻¹ × 100 g⁻¹ at rest and 58.4 ml × min⁻¹ × 100 g⁻¹ during exercise. CF was found to average 6.2 ml × min⁻¹ × 100 g⁻¹ at rest and increased to 9.2 ml × min⁻¹ × 100 g⁻¹ during exercise. CF was sufficient to cover the metabolic demand of resting muscle. During exercise the O₂-uptake ( ) of the distal muscle portion was increased 13.4 fold in comparison to a 3.1 fold increase in the proximal muscle portion. The average contractile power decreased by 46%. Additional infusion of adenosine into the distal artery resulted in an increase of CF to 11.4 ml × min⁻¹ × 100 g⁻¹ and of orthograde flow to 71 ml × min⁻¹ × 100 g⁻¹. The average contractile power of the muscle increased by 13%. Both orthograde flow and CF were found to decrease with increasing muscle load. But this decrease was significantly more pronounced in the case of CF especially at a. lower range of loads. It is concluded that after acute occlusion of orthograde flow, CF is limited by the number, the size and the dilatory capacity of precapillary network vessels. Furthermore, CF is influenced considerably by changes of extravascular support. Presented in part at the 43rd Meeting of the Deutsche Physiologische Gesellschaft [9] and at the XXVI International Congress of Physiological Sciences, New Delhi [6] Supported by the Deutsche Forschungsgemeinschaft (Hi 137/6)     

A novel and low-complexity peak detection algorithm for heart rate estimation from low-amplitude photoplethysmographic (PPG) signals

Abstract

Low-amplitude PPG signals are more affected by noise contamination and other undesirable effects because the signal strength is comparable to noise power. Although several authors claim that decreases in the amplitude of the PPG wave should be addressed from signal acquisition and conditioning stages such decreases can also be associated with changes in the patient condition. In that instance, it is important to ensure continuous and reliable HR monitoring which, in turn, depends on how robust is the peak detection method. Numerous efforts have been made to develop algorithms for accurate PPG peak detection under high motion artefact conditions. However, little has been done regarding peak detection in low-amplitude PPG signals. In an attempt to address this issue, a novel and simple peak detection algorithm for PPG signals was proposed. Results show that our method could be a good contribution for robust strategies that can dynamically adapt their peak detection method to circumstances in which a decrease in the amplitude of the PPG signal is expected. Still, more extensive testing under a wide range of conditions (e.g. intensive physical exercise) is needed to perform a rigorous validation.     

Mechanical sensitivity of regenerating myelinated skin and muscle afferents in the cat

These experiments describe the responses of myelinated skin and muscle afferent nerve fibres at a neuroma to stretch, local pressure and vibration in the anaesthetised cat. The sural nerve and the nerve supplying the medial gastrocnemius were studied. Neuroma formation was encouraged by placing the cut end of the nerve in a cuff made of synthetic material (Gore-tex). By 6 days after nerve section, the two nerves contained mechanically sensitive afferents. No motor fibres appeared to be mechanically sensitive. Mechanically sensitive sural afferents responded to ramp stretch of the nerve, applied at the cuff, with a single impulse or brief burst of impulses. The majority of gastrocnemius afferents responded to stretch with slowly adapting trains of impulses. Many muscle group II afferents exhibited a steady resting discharge, while group I afferents had an intermittent or bursting resting discharge or were silent. Those group I axons which showed resting activity had a low stretch threshold and were probably Ia fibres. Many of the silent units were also stretch sensitive. It is proposed that the spontaneously active units and silent units with low stretch thresholds were Ia fibres, while silent units with high stretch thresholds were Ib fibres. Both sural and gastrocnemius afferents responded to locally applied vibration. The mean peak response frequency for sural units was 170 Hz (± 70 Hz SD). For gastrocnemius units it was 325 Hz (± 86 Hz SD). Group I muscle afferents responded to higher frequencies of vibration than group II afferents. In four experiments the nerve was treated at a site a few millimetres proximal to the point of section with the axonal transport blocker colchicine. Twenty-five millimolar colchicine blocked impulse conduction at its point of application. Nevertheless, mechanically sensitive areas developed in the nerve just proximal to the treated region. Ten millimolar colchicine did not block impulse conduction, but led to dispersion of mechanosensitive areas to more proximal regions of the nerve. This result suggests that the disruption of orthograde axonal transport by colchicine leads to development of mechanically sensitive areas in axons further back from their cut ends. Local application of the drugs succinyl choline, tetra-ethyl ammonium and gadolinium had no effect on levels of resting activity or on mechanical sensitivity of afferents in the cuff. The potassium channel blocker 4-aminopyridine, on the other hand, produced an increase in the levels of resting activity and in the stretch responses of afferents. None of these drugs induced any activity in motor axons. It is proposed that mechanical sensitivity is induced at the sprouting tips of sensory axons by a substance or substances transported down the axon from the cell body. Such a conclusion implies that some of the response properties of normal mechanoreceptors in skin and muscle may be the result of influences exerted by the cell body on the peripheral terminal membranes. This conclusion has important implications for understanding transduction mechanisms and the development of somatic receptors, and for interpretation of receptor responses following nerve section and reinnervation or cross-reinnervation.     

Post-exercise facilitation of compound muscle action potentials evoked by transcranial magnetic stimulation in healthy subjects

Post-exercise facilitation (PEF) of motor evoked potentials (MEPs) was studied by transcranial magnetic stimulation in 15 healthy subjects following standardized and controlled isometric contraction of the biceps brachii muscle. PEF was highly dependent on the time delay (TD) from muscle relaxation to delivery of the magnetic stimulus and only to a minor degree on the duration of the maintained muscular contraction of 2, 4, and 6 s. In addition, PEF was unaffected by the contraction levels of 25%, 50%, and 100% of maximal voluntary contraction (MVC). There was a linear relationship between the log amplitude of the post-exercise MEPs and the TD. The time point at which PEF had vanished was calculated to be 15.2 s. In order to challenge the question whether segmental and/or suprasegmental mechanisms are primarily responsible for PEF, MEPs and H-reflexes were recorded from the soleus muscle following a sustained plantar flexion at the ankle joint in three healthy subjects. PEF of MEPs was present at a TD of 1000 ms following a sustained contraction of 6 s at a level of 50% of MVC. It was accompanied by a pronounced decrease in the soleus H-reflex amplitude at a TD of 1000 ms.     

A comparison of photoplethysmography and ECG recording to analyse heart rate variability in healthy subjects

Measures of heart rate variability (HRV) are widely used to assess autonomic nervous system (ANS) function. The signal from which they are derived requires accurate determination of the interval between successive heartbeats; it can be recorded via electrocardiography (ECG), which is both non-invasive and widely available. However, methodological problems inherent in the recording and analysis of ECG traces have motivated a search for alternatives. Photoplethysmography (PPG) constitutes another means of determining the timing of cardiac cycles via continuous monitoring of changes in blood volume in a portion of the peripheral microvasculature. This technique measures pulse waveforms, which in some instances may prove a practical basis for HRV analysis. We investigated the feasibility of using earlobe PPG to analyse HRV by applying the same analytic process to PPG and ECG recordings made simultaneously. Comparison of 5-minute recordings demonstrated a very high degree of correlation in the temporal and frequency domains and in nonlinear dynamic analyses between HRV measures derived from PPG and ECG. Our results confirm that PPG provides accurate interpulse intervals from which HRV measures can be accurately derived in healthy subjects under ideal conditions, suggesting this technique may prove a practical alternative to ECG for HRV analysis. This finding is of particular relevance to the care of patients suffering from peripheral hyperkinesia or tremor, which make fingertip PPG recording impractical, and following clinical interventions known to introduce electrical artefacts into the electrocardiogram.     

Effects of experimental muscle pain on shoulder-abduction force steadiness and muscle activity in healthy subjects

We previously demonstrated that the steadiness of shoulder abduction is reduced in patients with subacromial impingement syndrome (SIS), which might be related to shoulder pain associated with the SIS. The aim of the present study was to examine the acute effects of experimental shoulder muscle pain on shoulder motor function in healthy subjects. The fluctuations in exerted force (force steadiness) and electromyographic (EMG) activity from eight shoulder muscles were determined during sub-maximal isometric and dynamic contractions with the shoulder abductors in nine healthy subjects (27.7 ± 4.2 years, mean ± 1 SD) before, during and after experimental pain induction. Experimental pain was induced by bolus injections of 6% hypertonic saline into the supraspinatus muscle. Experimental muscle pain reduced shoulder-abduction force steadiness on average by 21% during isometric contractions (P = 0.012) and tended to do so during concentric contractions (P = 0.083). Middle deltoid, and infraspinatus and lower trapezius muscle activity increased (3–5% EMG_max) during isometric and concentric contractions, respectively (P < 0.05). Thus, experimental shoulder muscle pain reduced the steadiness of isometric shoulder abduction and caused small changes in the abduction activation strategy. The observed effects of experimental pain on shoulder motor function differed from that observed previously in patients with SIS and chronic pain during the same types of contractions. A possible explanation may be that, even though the adopted experimental pain-paradigm may reflect the SIS in terms of the painful structures, it might not reflect the adaptations in the central nervous system seen with chronic pain.     

造影红细胞对剪切流中肿瘤细胞黏附的影响

目的研究造影红细胞对剪切流环境中白细胞介导肿瘤细胞在内皮细胞上黏附的影响。方法在平行平板流动腔中加入20%比容的造影红细胞,分析不同剪切率(62.5、100、200 s-1)下内皮细胞上黏附白细胞数目、肿瘤细胞与黏附白细胞的碰撞事件以及稳定黏附肿瘤细胞数目的变化。结果造影红细胞促进白细胞在内皮细胞上黏附,增加肿瘤细胞与黏附白细胞的碰撞频率,并最终促进肿瘤细胞在内皮细胞上的黏附,且这一现象在高剪切率(200 s-1)下更为明显;但造影红细胞对肿瘤细胞的黏附效率并无显著影响。结论剪切流中造影红细胞的存在对肿瘤细胞在内皮细胞上的黏附起到促进作用,研究结果为探索癌症治疗方法提供理论基础。     

The mechanical effects of contractions on blood flow to the muscle

To determine whether muscle contractions can increase muscle blood flow independently from metabolic factors, we isolated the vasculature of the left diaphragm or gastrocnemius muscle of anesthetized and mechanically ventilated dogs. Arterial blood flow was controlled with a constant pressure source and the arterial pressure (P _a) was decreased in steps to obtain pressure-flow relationships (P- ) . The local vasculatures were maximally dilated with nitroprusside [mean (SD)114.0 (32.0) g·min^–1], adenosine [1.43(0.41) mmol·l^–1·min^–1], and acetylcholine [l.43(0.41) mmol·l^–1·min^–1] and theP- with and without spontaneous contractions (n = 6) , stimulated twitches (n = 12, 2–4 Hz), or tetanic trains (n = 7, 25 Hz) in the diaphragm and stimulated twitches (n = 6, 2–4 Hz), or tetanic contractions (n = 6, 12–16 trains) in the gastrocnemius were compared. The pressure axis intercept decreased (P < 0.5) with spontaneous contractions in the diaphragm and the slope did not change. AtP _a of 13.3 kPa, flow increased from 36.2 (34.9) to 43.9 (38.2) ml·min^–1·100 g^–1 (P < 0.05). During twitch contractions, the slope and intercept of theP- were not significantly different from vasodilatation alone, but the flow at a pressure of 13.3 kPa increased slightly. In the gastrocnemius (n = 6), continuous and intermittent tetanic contractions did not affectP- or flow atP _a of 100 mmHg (n = 6). Furthermore, increasing venous pressure to 6.7 kPa did not affect flow in this muscle. We conclude that the muscle pump has only a small direct effect on muscle blood flow and its main effect is to reduce venous pressures.     

Linear and nonlinear analysis of blood flow in healthy subjects and in subjects with Raynaud's phenomenon.

The paper presents analyses of the dynamics contained in the blood flow signals measured on healthy subjects and on subjects with primary Raynaud's phenomenon. Different signal processing methods are presented and discussed. The dynamics was evaluated in the time and frequency domains and in phase space. Additionally, changes in the basal value during temperature provocation were studied using multiresolution analysis. The analyses demonstrate differences between the blood flow dynamics in healthy subjects and subjects with Raynaud's phenomenon. Moreover, the observed decrease in the amplitude of oscillation in regions approximately 0.04 Hz and approximately 0.1 Hz suggests an impairment in the neurogenic and the myogenic regulation of the blood flow. The administration of nifedipine in subjects with Raynaud's phenomenon results in an increase in the basal value and in the amplitude of the blood flow component oscillating with the heart rate. However, it does not restore the dynamics to that found in healthy subjects.     

Non-invasive continuous estimation of blood flow changes in human patellar bone

A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component—which is related to the relative vascularization of the tissue—and a pulsatile (AC) component—which is synchronous with the pumping action of the heart. The PPG probe was applied on the skin over the patella. The probe uses near-infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respectively. Twenty healthy subjects were studied and arterial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC component of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.     

Effects of hypoxia on cerebral and muscle haemodynamics during knee extensions in healthy subjects

A hypoxic model was used to investigate changes in localized cerebral and muscle haemodynamics during knee extension (KE) in healthy individuals. Thirty-one young healthy volunteers performed one set of KE until failure under hypoxia (14 % O₂) or normoxia (21 % O₂) at 50, 75 or 100 % of 1 repetition maximum, in random order, on three occasions. Prefrontal cerebral and vastus lateralis muscle oxygenation and blood volume (Cox, Mox, Cbv and Mbv, respectively) were recorded simultaneously by near-infrared spectroscopy. Hypoxia induced significant declines in Cox [?0.017 ± 0.016 optical density (OD) units] and Mox (?0.014 ± 0.026 OD units) and increases in Cbv (0.017 ± 0.027 OD units) and Mbv (0.016 ± 0.023 OD units) at rest. Hypoxia significantly reduced total work (TW) performed during KE at each exercise intensity. Cox, Cbv, Mox, and Mbv changes during KE did not differ between normoxia and hypoxia. Correlations between TW done and Cox changes under normoxia (r = 0.04, p = 0.182) and hypoxia (r = 0.05, p = 0.122) were not significant. However, TW was significantly correlated with Mox under both normoxia (R ² = 0.24, p = 0.000) and hypoxia (R ² = 0.15, p = 0.004). Since changes in Cox and Mox reflect alterations in the balance between oxygen delivery and extraction in these tissues, which, in the brain, is an index of neuronal activation, we conclude that: (1) limitation of KE performance was mediated peripherally under both normoxia and hypoxia, with no additional effect of hypoxia, and (2) because of the low common variance with Mox additional intramuscular factors likely play a role in limiting KE performance.